Cyclopropenimine-Mediated CO Activation for the Synthesis of Polyurethanes and Small-Molecule Carbonates and Carbamates.

Carbon dioxide (CO) is an abundant C1 feedstock with tremendous potential to produce versatile building blocks in synthetic applications. Given the adverse impact of CO on the atmosphere, it is of paramount importance to devise strategies for upcycling it into useful materials, such as polymers and fine chemicals. To activate such stable molecule, superbases offer viable modes of binding to CO.

Ring-Opening Polymerization of Cyclic Esters and Carbonates with (Thio)urea/Cyclopropenimine Organocatalytic Systems.

Organocatalyzed ring-opening polymerization is a powerful tool for the synthesis of a variety of functional, readily degradable polyesters and polycarbonates. We report the use of (thio)ureas in combination with cyclopropenimine bases as a unique catalyst for the polymerization of cyclic esters and carbonates with a large span of reactivities. Methodologies of exceptionally effective and selective cocatalyst combinations were devised to produce polyesters and polycarbonates with narrow dispersities ( = 1.

pH-Responsive Polymeric Micelle Dynamic Complexes for Selective Killing of .

, the world's most common chronic infection-causing pathogen, is responsible for causing gastric ulcers, the fourth-leading cause of cancer-related death globally in 2020. In recent years, the effectiveness of the current treatment regimen (two antibiotics and one proton pump inhibitor) has often been plagued with problems such as resistance and the undesired elimination of commensal bacteria. Herein, we report the synthesis of block and random copolycarbonates, functionalized with cationic guanidinium and anionic acetate functional groups, aimed at selectively killing in the acidic environment of the stomach, while remaining nontoxic to the commensal bacteria in the gut.

Artificial intelligence driven design of catalysts and materials for ring opening polymerization using a domain-specific language.

Advances in machine learning (ML) and automated experimentation are poised to vastly accelerate research in polymer science. Data representation is a critical aspect for enabling ML integration in research workflows, yet many data models impose significant rigidity making it difficult to accommodate a broad array of experiment and data types found in polymer science. This inflexibility presents a significant barrier for researchers to leverage their historical data in ML development.

Nanocomplexes of Biodegradable Anticancer Macromolecules: Prolonged Plasma Half-Life, Reduced Toxicity, and Increased Tumor Targeting.

Anticancer drug resistance is a large contributing factor to the global mortality rate of cancer patients. Anticancer macromolecules such as polymers have been recently reported to overcome this issue. Anticancer macromolecules have unselective toxicity because they are highly positively charged.

Pharmacokinetics of ciprofloxacin and fluocinolone acetonide otic solution in pediatric patients.

Purpose: To describe the pharmacokinetics (PK) of ciprofloxacin 0.3 % and fluocinolone acetonide 0.025 % otic solution (CIPRO+FLUO), ciprofloxacin 0.

Efficacy and Safety of Ciprofloxacin Plus Fluocinolone Acetonide Among Patients With Acute Otitis Externa: A Randomized Clinical Trial.

Importance: Ciprofloxacin, 0.3%, plus fluocinolone acetonide, 0.025%, otic solution seems to be efficacious and safe in treating acute otitis externa (AOE) compared with ciprofloxacin, 0.

Simple and Efficient Synthesis of Functionalized Cyclic Carbonate Monomers Using Carbon Dioxide.

Aliphatic polycarbonates represent an important class of materials with diverse applications ranging from battery electrolytes, polyurethane intermediates, and materials for biomedical applications. These materials can be produced via the ring-opening polymerization (ROP) of six- to eight-membered cyclic carbonates derived from precursor 1,3- and 1,5-diols. These diols can contain a range of functional groups depending on the desired thermal, mechanical, and solution properties.

A Cation-Dependent Dual Activation Motif for Anionic Ring-Opening Polymerization of Cyclic Esters.

A new organocatalyst for the ring-opening polymerization of lactones has been identified. Under the tested conditions, the anions of 2,2'-bisindole promote fast, living polymerizations (as short as 10 ms) which are selective for chain elongation over transesterification (Đ ≤ 1.1).

Safety and immunogenicity of an investigational quadrivalent meningococcal tetanus toxoid conjugate vaccine (MenACYW-TT) co-administered with routine pediatric vaccines in infants and toddlers: A Phase II study.

Background: The MenACYW-TT conjugate vaccine is approved for prevention of invasive meningococcal disease (IMD) as a single dose in individuals ≥2 years of age in the United States and ≥12 months in EU and some other countries. This Phase II study evaluated the safety and immunogenicity of this vaccine and of concomitant pediatric vaccines in infants/toddlers (6 weeks-15 months of age).

Methods: Five schedules of the MenACYW-TT conjugate vaccine were evaluated in the United States: 2, 4, 6, and 12 months; 2, 4, 6, and 15 months; 2, 4, and 12 months; 6 and 12 months; and 12 months alone.

Infant Formula with Added Bovine Milk Fat Globule Membrane and Modified Iron Supports Growth and Normal Iron Status at One Year of Age: A Randomized Controlled Trial.

Inclusion of bovine-derived milk fat globule membrane (bMFGM) or bMFGM components in infant formulas (IFs) may support healthy brain development. This double-blind, prospective trial evaluated growth, tolerance, and iron status in infants receiving added bMFGM and modified protein, iron, and arachidonic acid (ARA) concentrations in IF. Healthy term infants were randomized to: control (marketed, routine cow's milk-based IF/100 kcal: 2.

Elucidating the anticancer activities of guanidinium-functionalized amphiphilic random copolymers by varying the structure and composition in the hydrophobic monomer.

Use of traditional anticancer chemotherapeutics has been hindered by the multifactorial nature of multi-drug resistance (MDR) development and metastasis. Recently, cationic polycarbonates were reported as novel unconventional anticancer agents that mitigated MDR and inhibited metastasis. The aim of this study is to explore structure-anticancer activity relationship.

Effects of Hydrophobicity on Antimicrobial Activity, Selectivity, and Functional Mechanism of Guanidinium-Functionalized Polymers.

In this study, a series of guanidinium-functionalized polycarbonate random co-polymers is prepared from organocatalytic ring-opening polymerization to investigate the effect of the hydrophobic side chain (ethyl, propyl, isopropyl, benzyl, and hexyl) on their antimicrobial activity and selectivity. Although the polymers exhibit similar minimum inhibitory concentrations, the more hydrophobic polymers exhibit a faster rate of bacteria elimination. At higher percentage content (20 mol%), polymers with more hydrophobic side chains suffer from poor selectivity due to their high hemolytic activity.

Accelerated antimicrobial discovery via deep generative models and molecular dynamics simulations.

The de novo design of antimicrobial therapeutics involves the exploration of a vast chemical repertoire to find compounds with broad-spectrum potency and low toxicity. Here, we report an efficient computational method for the generation of antimicrobials with desired attributes. The method leverages guidance from classifiers trained on an informative latent space of molecules modelled using a deep generative autoencoder, and screens the generated molecules using deep-learning classifiers as well as physicochemical features derived from high-throughput molecular dynamics simulations.

Cationic polymer synergizing with chemotherapeutics and re-purposing antibiotics against cancer cells.

Chemotherapy is one of the most effective treatments for cancer. However, toxicity and the development of drug resistance have become the major hurdles to the commonly used chemotherapeutics such as doxorubicin and paclitaxel. Antibiotics have also been used as anti-cancer drugs due to their anti-proliferative and cytotoxic effects.

Selective Chemical Upcycling of Mixed Plastics Guided by a Thermally Stable Organocatalyst.

Chemical recycling of plastic waste represents a greener alternative to landfill and incineration, and potentially offers a solution to the environmental consequences of increased plastic waste. Most plastics that are widely used today are designed for durability, hence currently available depolymerisation methods typically require harsh conditions and when applied to blended and mixed plastic feeds generate a mixture of products. Herein, we demonstrate that the energetic differences for the glycolysis of BPA-PC and PET in the presence of a protic ionic salt TBD:MSA catalyst enables the selective and sequential depolymerisation of these two commonly employed polymers.

Biodegradable Cationic Polycarbonates as Vaccine Adjuvants.

In this study, biodegradable cationic polycarbonate and polylactide block copolymers were synthesized and successfully used as novel vaccine adjuvants to provide enhanced anticancer immunity. The polymers formed nanoparticles with the model vaccine, ovalbumin (OVA), and the immunostimulant toll-like receptor 3 agonist poly(I:C) (a synthetic analog of the double-stranded RNA). Higher uptake of poly(I:C) by the bone marrow-derived dendritic cells and macrophages and OVA by dendritic cells was observed when delivered using the polymer adjuvant.

Carboxylic acid-functionalized polycarbonates as bone cement additives for enhanced and sustained release of antibiotics.

Despite the good clinical outcomes of total joint replacements, prosthetic joint infections still remain a significant cause of implant failure. Primary prophylaxis is key to stemming this burgeoning problem and its associated complications. In this study, a series of bone cement formulations with enhanced antibacterial performance have been developed through the addition of carboxylic acid-functionalized polycarbonate block copolymers to commercially available bone cement.

The effect of solvent quality on pathway-dependent solution-state self-assembly of an amphiphilic diblock copolymer.

The cholesterol-functionalized polycarbonate-based diblock copolymer, PEG--P(MTC-Chol), forms pathway-dependent nanostructures via dialysis-based solvent exchange. The initial organic solvent that dissolves or disperses the polymer dictates a self-assembly pathway. Depending upon the initial solvent, nanostructures of disk-like micelles, exhibiting asymmetric growth and hierarchical features, are accessible from a single amphiphilic precursor.

A Macromolecule Reversing Antibiotic Resistance Phenotype and Repurposing Drugs as Potent Antibiotics.

In order to mitigate antibiotic resistance, a new strategy to increase antibiotic potency and reverse drug resistance is needed. Herein, the translocation mechanism of an antimicrobial guanidinium-functionalized polycarbonate is leveraged in combination with traditional antibiotics to afford a potent treatment for drug-resistant bacteria. Particularly, this polymer-antibiotic combination approach reverses rifampicin resistance phenotype in demonstrating a 2.

Combination of guanidinium and quaternary ammonium polymers with distinctive antimicrobial mechanisms achieving a synergistic antimicrobial effect.

The increasing emergence and spread of antimicrobial resistance are urgent and important global challenges today. The clinical pipeline is lacking in innovative drugs that avoid the development of drug resistance. Macromolecular antimicrobials kill bacteria and fungi through physical disruptions to the cell membrane, which is difficult for microbes to overcome.

Immunogenicity, safety and inter-lot consistency of a meningococcal conjugate vaccine (MenACYW-TT) in adolescents and adults: A Phase III randomized study.

Background: MenACYW-TT is an investigational quadrivalent (serogroups A, C, W and Y) meningococcal conjugate vaccine that is being developed for protection against invasive meningococcal disease.

Methods: In this Phase 3, blinded, randomized study, 3344 meningococcal vaccine-naïve 10-55-year-olds were randomized (3:3:3:2) to receive one of three lots of MenACYW-TT or licensed quadrivalent meningococcal conjugate vaccine, MCV4-DT (NCT02842853). Antibody titers were assessed by human and rabbit complement serum bactericidal antibody assays.